Using both clinical and experimental approaches, we propose to study the alteration of the blood-retinal barrier (BRB) which occures in the early stages of retinal involvement in diabetes: 1. Vitreous fluorophotometry will be further standardized in normals and in diabetes as a routine procedure for evaluation of the BRB in retinal disease. The role of aging in normal individuals on the BRB will be examined. 2. Vitreous fluorophotometry (V.F.) examination and direct sampling of the vitreous using micromethods in experimental diabetes in situation of selective alteration of the BRB transport processes, and in situations of alteration of the junctional structures are expected to contribute significantly to our understanding of the intraocular fluorescein dynamics in retinal diseases and in diabetes. The results from V.F. and from direct sampling will be correlated. 3. Ulstrastructural tracer techniques will be applied to the same experimental situations in order to localize the alterations of the BRB. 4. We shall examine in experimental diabetes the correlations between alteration of the blood-retinal barrier and experimental induced variations in insulin, glucagon, and growth hormone. 5. We shall examine by vitreous fluorophotometry the early breakdown of BRB that occurs in diabetes mellitus in a series of diabetic patients and compare the values obtained with degree of diabetic metabolic control and development of retinal lesions. 6. In order to improve and test the use of vitreous fluorophotometry for early detection of retinal involvement in diabetes an attempt will be made to develop vitreous fluorophotometry glucose tolerance test. The ultimate goal of this proposal is to define the clinical, pathological, and physiological aspects of the early alteration of the BRB, which occurs in diabetes before any other clinically detectable lesions are visible in the retina and which play a fundamental role in the development of diabetic retinopathy.